Resolution of Proteins in the Kidney Stone Matrix Using High-Performance Liquid Chromatography

Sugimoto, Toshikado; Funae, Yoshihiko; Rübben, H.; Nishio, S.; Hautmann, Richard E.; Lutzeyer, W

doi:10.1159/000472531

Cited by 26 publications

(15 citation statements)

References 18 publications

(28 reference statements)

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“…B , SDS-PAGE following fractionation using off-gel iso-electric focusing of control and stone former pools. The lanes (1–12) represent the fractions. C , Representative chromatogram showing total base peak intensity (BPI) of fraction 5 of stone formers ( left panel) and non-stone formers ( right panel) in experiment 2.…”

Section: Resultsmentioning

confidence: 99%

“…The majority (∼80%) of urinary tract stones are predominantly calcium oxalate in composition (3). The etiology of kidney stone formation is unknown, but proteins have been implicated in crystal nucleation, regulation of crystal growth and aggregation, and regulation of adhesion to the renal tubule and urothelium (4–6). Thus, it is likely that there may be proteins in urine that either promote stone formation in stone formers or inhibit stone formation under normal circumstances.…”

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confidence: 99%

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Label-free Quantitative Proteomics Reveals Differentially Regulated Proteins Influencing Urolithiasis

Wright

Howles

Kessler

et al. 2011

Molecular & Cellular Proteomics

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Urinary proteins have been implicated as inhibitors of kidney stone formation (urolithiasis). As a proximal fluid, prefiltered by the kidneys, urine is an attractive biofluid for proteomic analysis in urologic conditions. However, it is necessary to correct for variations in urinary concentration. In our study, individual urine samples were normalized for this variation by using a total protein to creatinine ratio. Pooled urine samples were compared in two independent experiments. Differences between the urinary proteome of stone formers and nonstone-forming controls were characterized and quantified using label-free nano-ultraperformance liquid chromatography high/low collision energy switching analysis. There were 1063 proteins identified, of which 367 were unique to the stone former groups, 408 proteins were unique to the control pools, and 288 proteins were identified for comparative quantification. Proteins found to be unique in stone-formers were involved in carbohydrate metabolism pathways and associated with disease states. Thirty-four proteins demonstrated a consistent >twofold change between stone formers and controls. For ceruloplasmin, one of the proteins was shown to be more than twofold up-regulated in the stone-former pools, this observation was validated in individuals by enzyme-linked immunosorbent assay. Moreover, in vitro crystallization assays demonstrated ceruloplasmin had a dose-dependent increase on calcium oxalate crystal formation. Taken together, these results may suggest a functional role for ceruloplasmin in urolithiasis.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Label-free Quantitative Proteomics Reveals Differentially Regulated Proteins Influencing Urolithiasis

Wright

Howles

Kessler

et al. 2011

Molecular & Cellular Proteomics

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“…Dawson et al [38] extracted calcium oxalate (8 stones) or calcium phosphate stones (2 stones) with 0.25M EDTA for 48h, and found variable amounts of protein; in some samples, protein bands were barely visible. Sugimoto et al [39] extracted stone proteins in saline by dialyzing against 0.1 M EDTA, and found protein levels were significantly increased in calcium phosphate (3 stones) over calcium oxalate stones, with an average extractible protein content of all stones of 1.6%.…”

Section: Discussionmentioning

confidence: 99%

Protein content of human apatite and brushite kidney stones: significant correlation with morphologic measures

et al. 2008

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Apatite and brushite kidney stones share calcium and phosphate as their main inorganic components. We tested the hypothesis that these stone types differ in the organic matrix present in the stones. Intact stones were intensively analyzed by micro-computed tomography (micro CT) for both morphology (including the volume of voids, i.e., regions without mineral) and mineral type. In order to extract all proteins present in kidney stones in soluble form we developed a three-step extraction procedure using the ground stone powder. Apatite stones had significantly higher levels of total protein content and void volume compared to brushite stones. The void volume was highly correlated with the total protein contents in all stones (r2=0.61, P<0.0001), and brushite stones contained significantly fewer void regions and proteins than did apatite stones (3.2±4.5% voids for brushite vs. 10.8±11.2% for apatite, P<0.005; 4.1±1.6% protein for brushite vs. 6.0±2.4% for apatite, P<0.03). Morphological observations other than void volume did not correlate with protein content of stones, and neither did the presence or absence of minor mineral components. Our results show that protein content of brushite and apatite stones is higher than was previously thought, and also suggest that micro CT-visible void regions are related to the presence of protein.

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“…Although not detected by Boyce, lipids have also been shown to be significant components of stone matrix [15]. Nonetheless, proteins comprise the major part of matrix, an observation confirmed by Sugimoto et al [16]. It was inevitable therefore that protein would tend to dominate the study of matrix, and consequently, considerably more is known about them than the other two principal groups, namely, lipids and glycosaminoglycans (GAGs).…”

Section: The Stonementioning

confidence: 99%

Nephrolithiasis: Molecular Mechanism of Renal Stone Formation and the Critical Role Played by Modulators

Aggarwal

Narula

Kakkar³

et al. 2013

BioMed Research International

259

232

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Urinary stone disease is an ailment that has afflicted human kind for many centuries. Nephrolithiasis is a significant clinical problem in everyday practice with a subsequent burden for the health system. Nephrolithiasis remains a chronic disease and our fundamental understanding of the pathogenesis of stones as well as their prevention and cure still remains rudimentary. Regardless of the fact that supersaturation of stone-forming salts in urine is essential, abundance of these salts by itself will not always result in stone formation. The pathogenesis of calcium oxalate stone formation is a multistep process and essentially includes nucleation, crystal growth, crystal aggregation, and crystal retention. Various substances in the body have an effect on one or more of the above stone-forming processes, thereby influencing a person's ability to promote or prevent stone formation. Promoters facilitate the stone formation while inhibitors prevent it. Besides low urine volume and low urine pH, high calcium, sodium, oxalate and urate are also known to promote calcium oxalate stone formation. Many inorganic (citrate, magnesium) and organic substances (nephrocalcin, urinary prothrombin fragment-1, osteopontin) are known to inhibit stone formation. This review presents a comprehensive account of the mechanism of renal stone formation and the role of inhibitors/promoters in calcium oxalate crystallisation.

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Resolution of Proteins in the Kidney Stone Matrix Using High-Performance Liquid Chromatography

Cited by 26 publications

References 18 publications

Label-free Quantitative Proteomics Reveals Differentially Regulated Proteins Influencing Urolithiasis

Label-free Quantitative Proteomics Reveals Differentially Regulated Proteins Influencing Urolithiasis

Protein content of human apatite and brushite kidney stones: significant correlation with morphologic measures

Nephrolithiasis: Molecular Mechanism of Renal Stone Formation and the Critical Role Played by Modulators

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